A 13-year-old neutered male Maltese dog presented to our hospital with lethargy and anorexia. Laboratory abnormalities included severe non-regenerative anemia (hematocrit, 12.9%; reticulocyte count 12.8 K/μL). The cytology of bone marrow revealed erythroid hypercellularity with mild myelofibrosis. Therefore, late-stage precursor-targeted immune-mediated anemia (PIMA) was diagnosed. Multimodal treatment including 2 immunosuppressant drugs (prednisolone and mycophenolate mofetil), antithrombic drug (clopidogrel), and blood transfusion was performed. The dog showed complete remission from PIMA, and the total duration of follow-up was 622 days. This is the first case report of canine PIMA managed successfully with prednisolone and mycophenolate mofetil in Korea.

Effects of a single IV administered therapeutic dose of vincristine sulfate on platelet numbers and function were evaluated in 16 clinically normal dogs over the 2 weeks after drug administration. Results were statistically compared with those of a previous control study in which the same 16 dogs were administered saline solution (IV), instead of vincristine. Of the 16 dogs, 8 were orally administered daily immunosuppressive doses of prednisone concurrently throughout the saline-control and vincristine study periods. Platelet numbers and mean platelet volume were measured, using an automated hematology analyzer. Platelet function was evaluated by turbidimetric measurement of platelet aggregation in response to collagen, platelet-activating factor, and adenosine diphosphate (ADP), and by clot retraction (diluted whole-blood method) and buccal mucosa bleeding time. Vincristine had a significant (P < 0.05) effect on circulating platelet numbers. Vincristine induced a transient mild decrease in platelet numbers, followed by a moderate increase in numbers, with peak platelet count observed 8 days after drug administration. Mean platelet volume was not significantly affected by administration of vincristine. Vincristine had no significant effects on platelet aggregation in response to collagen, low or high doses of platelet-activating factor, and a high dose of ADP. The maximal degree of platelet aggregation attained in response to a low dose of ADP was not significantly affected by prior administration of vincristine. The maximal rate of platelet aggregation induced by a low dose of ADP after vincristine administration, however, was significantly (P < 0.05) lower than the rate of aggregation induced by a similar dose of ADP in the previous control study. Vincristine had no significant effects on clot retraction and bleeding time. Prednisone did not significantly affect platelet numbers and function, and did not modify vincristine's effects on the same variables.

Five cats were treated with an azathioprine suspension (2.2 mg/kg of body weight on alternate days) and 2 cats were given vehicle (controls) for 9 weeks. Complete blood and platelet counts and serum biochemistry variables were monitored weekly. Bone marrow aspirates were evaluated every 3 weeks, and core bone marrow biopsy was performed at the end of the study. Profound neutropenia (< 600 cells/microliter) was observed in all treated cats, and 1 cat developed pancytopenia. Treatment was discontinued if the WBC count was < 3,000 cells/microliter. Four weeks after discontinuation of azathioprine, 1 treated cat again was given azathioprine at a lower dosage (1.1 mg of azathioprine/kg on alternate days) and neutropenia recurred within 2 weeks. During treatment, 3 cats developed thrombocytosis, and 2 developed thrombocytopenia. In 4 of 5 cats, neutropenia and thrombocytopenia resolved when azathioprine was discontinued. Bone marrow cytologic examination during treatment revealed reduction of the neutrophil line, with relative increase in monocytes. Core bone marrow biopsy at the completion of the study revealed hypocellular marrow with marked decrease in the myeloid series in cats given azathioprine. One of the cats that was treated with azathioprine had a hyperceullar marrow with increased numbers of mature granulocytes and precursors; however, azathioprine had been discontinued 3 weeks prior to biopsy. Alterations in serum biochemical variables were not associated with azathioprine. Two cats that were treated with azathioprine developed respiratory tract infections, and 1 of them was euthanatized during the study.

Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 X 10(4) virulent Brucella abortus, caused significant (P < 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P < 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P < 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P < 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P < 0.01) diminished. The increase in numbers of B abortus in organs of irradiated mice that began after the third week coincided with recovery of the immune response and an increase in numbers of neutrophils and monocytes in the infected organs. The course of B abortus infection was not substantially altered during the first 11 days after inoculation in mice infected at the height of a profound monocytopenia and neutropenia induced by azathioprine, a drug that by itself failed to activate macrophages. We hypothesized that, in irradiated mice, a rapid radiation-induced activation of resident macrophages to a brucellacidal state was coupled with an absence of newly formed monocytes in which virulent strains of B abortus could establish persistent infection, and that as susceptible monocytes emerged in mice recovering from the effects of irradiation, chronic infection became established.

Pseudorabies is a porcine herpesvirus of major importance in the swine industry. Isoprinosine is an immunomodulating drug that has been shown to be beneficial in treating herpesvirus infections. Twenty-four 7-week-old pigs were allotted within litters to 1 of 4 groups: control, isoprinosine (ISO), pseudorabies virus (PRV), or isoprinosine and pseudorabies virus (ISO-PRV). Isoprinosine was administered daily for 16 days to the ISO and ISO-PRV groups (75 mg/kg of body weight/day, PO). Immunity in pigs in the PRV and ISO-PRV groups was challenged with pseudorabies virus (10(5) TCID50 units) on day 4. Rectal temperatures and viral excretion were monitored daily; total and differential leukocyte counts, lymphocyte response to mitogens, and interleukin-2 production were monitored every 4 days. Pigs challenge-inoculated with pseudorabies virus became ill, with the ISO-PRV group most severely affected. Rectal temperatures were high (P less than 0.05) in virally challenged pigs on days 5 to 12 and 14 to 16; isoprinosine did not alter this effect. Pseudorabies virus-infected pigs had leukocytosis (P less than 0.05) on days 12 and 16, primarily caused by neutrophilia. Concanavalin A-stimulated lymphocyte proliferation was decreased (P less than 0.06) in both PRV and ISO-PRV groups on day 12, compared with control pigs, but only in the PRV group on day 16. Pokeweed mitogen-stimulated lymphocyte proliferation was decreased (P less than 0.02) in ISO-PRV pigs on day 8 of the experiment. Interleukin-2 concentrations, pooled over all sampling days, were decreased (P less than 0.03) in pseudorabies virus-infected pigs. Viral excretion was not altered by isoprinosine treatment. These data suggest that pseudorabies virus infection decreased lymphocyte proliferative responses and interleukin-2 prodcution in pigs, and that isoprinosine did not mitigate these effects.

Objective-To use in vitro assays to evaluate the effects of a novel immunosuppressive agent, FTY720, on biological functions (migration, phagocytosis, and production of reactive-oxygen species ROS) of feline peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline peripheral neutrophils. Sample Population-Peripheral neutrophils obtained from 8 healthy cats. Procedure-Peripheral neutrophils were isolated from blood samples obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720-P). A fluorescence-based in vitro evaluation of migration was performed. Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color flow cytometry system. Samples of whole blood obtained from the cats were incubated with various concentrations of FTY720-P, fluorescein-labeled Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by use of propidium iodide staining. Results-Addition of FTY720-P caused a slight nonsignificant decrease in phagocytosis and production of ROS by feline peripheral neutrophils. Migration activity of feline peripheral neutrophils was significantly increased by the addition of FTY720-P. Addition of FTY720-P at concentrations considered for clinical use did not increase the death rate of feline peripheral neutrophils. Conclusions and Clinical Relevance-FTY720 does not inhibit critical functions of feline peripheral neutrophils in vitro.

Pharmacokinetic variables were calculated from time-concentration data obtained after IV (10 mg/kg of body weight; n = 9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (+/- SD) pharmacokinetic variables were as follows: half life of distribution, 0.96 (+/- 0.7) hours; half life of elimination, 7.71 (+/- 2.6) hours; volume of distribution at steady state, 4.47 (+/- 2.22) L/kg; volume of the central compartment, 1.71 (+/- 0.78) L/kg; and systemic clearance, 8.95 (+/- 2.7) ml/kg/min. Oral bioavailability was: overall 57 (+/- 19) %; group A, 44 (+/- 11) %; group B, 78 (+/- 15) %; group C, 48 (+/- 6) %. Time to peak concentration was 3.55 (+/- 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (+/- 78.4) ng/ml; group B, 640.7 (+/- 174.6) ng/ml; and group C, 2,344 (+/- 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.

The influence of immunosuppression by T-2 mycotoxin on the fungal disease aspergillosis was investigated in rabbits. Four groups of rabbits (groups 1A, 1B, 3A, and 3B) were given 0.5 mg of T-2 toxin/kg of body weight/day, PO; in addition, rabbits of groups 3A and 3B were exposed to aerosols of Aspergillus fumigatus conidia from days 7 through 16. Rabbits of groups 2A and 2B were exposed to A fumigatus aerosols, but were not given T-2 toxin, and rabbits of group 0 served as controls. Two rabbits of group 1A, 1 rabbit of group 1B, and 1 rabbit of group 3A died before scheduled necropsy. Rabbits of groups 1A, 2A and 3A were killed and necropsied on day 17, and the remaining rabbits (groups 0, 1B, 2B, and 3B) were killed and necropsied on day 28. Changes caused by T-2 toxin included leukopenia, marginal anemia, and increased number of and morphologic changes in nucleated erythrocytes by day 21, followed by a regenerative hematologic response. Serum alkaline phosphatase and sorbitol dehydrogenase activities and antibody response to A fumigatus (as measuredby an indirect hemagglutination test) were decreased by T-2 toxin ingestion. Rabbits with aspergillosis had leukocytosis, increased PCV, and increased antibody response to A fumigatus. Histologic lesions consisting of centrilobular hepatocellular swelling, portal and periportal fibrosis, and lymphocyte necrosis and/or depletion within secondary lymphoid tissue were observed in most rabbits treated with T-2 toxin. Normal defense mechanisms against A fumigatus infection were compromised by T-2 treatment, as evidenced by the severity and extent of lung lesions, greater number of hyphal elements observed, and greater number of colonies of A fumigatus isolated from rabbits of groups 3A and 3B. There were no significant changes in group-0 rabbits.

The effect of Fusarium-produced T-2 toxin on tumor growth was evaluated in ICR, CFW, and C57B6/6 mice inoculated with murine sarcoma, Ehrlich ascites carcinoma, or B16F1 melanoma tumor cell lines. Mice were given T-2 toxin intragastrically either at the rate of 2 mg of toxin/kg of body weight daily for 5 days or a single dosage of 4 mg of toxin/kg and were inoculated SC with tumor cells 1 or 2 days after administration of toxin. Tumor growth was assessed 15 to 41 days after tumor challenge by determining the frequency of tumor development and tumor weights. Significant increases in the frequency of development of murine sarcoma (P < 0.005). Ehrlich ascites carcinoma (P < 0.01), and B16F1 melanoma tumors (P < 0.05) were detected in toxin-treated mice, compared with control mice. Murine sarcoma and B16F1 melanoma tumor weights also were significantly (P < 0.01) higher in toxin-treated mice. The effect of T-2 toxin on tumor growth was more marked after 5 daily treatments than after a single dose.

Conditions necessary for establishment of a graft, posttransplant supportive care and complications, and lymphohematopoietic reconstitution after bone marrow transplantation were evaluated in 7 cats. Donor-recipient pairs were selected on the basis of low mutual reactivity in one-way mixed lymphocyte reactions. Before transplantation, cats were given marrow ablative (7 Gray) total-body gamma irradiation. Cyclosporine A was administered to cat 7, which was given marrow from an unrelated donor. Rapid hematologic recovery was attained in 5 of 5 (cats 1 to 5) sibling bone marrow recipients and 1 (cat 7; cyclosporine A-treated) of 2 recipients from unrelated donors. Lymphocyte recovery was prolonged, requiring up to 100 days to attain reference concentrations. Lymphocyte blastogenic responses were below reference range in 2 of 3 cats (cats 1 and 3) examined approximately 1 to 3 months after transplantation. Serum IgG concentrations determined 1 to 6 months after transplantation were within reference range in cats 1 to 5 which were given sibling bone marrow. Fatal infections did not develop in cats that had established grafts. Antimicrobial-responsive fevers did develop, but were generally detected only when granulocyte counts were low (< 1 X 10(9) cells/L). Clinical signs of disease in the immediate posttransplant period consisted of hepatic lipidosis (fatal) in cat 4, hepatitis (mild graft-vs-host disease) in cat 3, and immune-mediated hemolytic anemia and thrombocytopenia in cat 7. Cats with hepatitis and immune-mediated disease responded to immunosuppressive therapy.